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Medical Countermeasures Against Chemical Threats

Cellular Respiration

Current Medical Countermeasures

Pretreatment and Post-Exposure Treatment

No pretreatment for cyanide poisoning is available and may not be practical. Since 1933, a Cyanide Antidote Kit has been marketed for use in the United States but, as a kit, it has never received formal regulatory approval by the Food and Drug Administration (FDA). The Cyanide Antidote Kit includes crushable ampules of amyl nitrite, for inhalation, and sodium nitrite and sodium thiosulfate, which are administered intravenously. The nitrites bind with hemoglobin in the blood to produce methemoglobin molecules. The methemoglobin then binds with cyanide to produce a much less toxic compound, cyanomethemoglobin, which is eventually eliminated from the body. Sodium thiosulfate, often referred to as a sulfur donor drug, converts cyanide into non-toxic thiocyanate, which is then excreted by the kidneys.

Use of the Cyanide Antidote Kit can be very effective as a post-exposure treatment for cyanide poisoning, but it carries the risk of toxic side effects. High levels of methemoglobin can be lethal. Determining the correct dose is especially challenging for treating pediatric casualties. Individuals with pre-existing glucose 6-phosphate deficiency (G6PD deficiency, the most common inherited enzyme deficiency in humans) have a risk of red cell hemolysis if given sodium thiosulfate. Individuals with renal deficiency or anemia could also suffer toxicity from the treatment. Concern has been raised over the ability to quantify predictably the amount of amyl nitrite that would be absorbed through inhalation.

Recently, FDA approved Cyanokit (hydroxocobalamin for injection) for the treatment of cyanide poisoning. It has not yet been determined how effective this new countermeasure would be in a mass casualty situation.

Administration of 10 percent (hyperbaric) oxygen is a major component in the treatment of cyanide poisoning and is typically used even before the administration of any cyanide antidotes. However, the value of hyperbaric oxygen has not been determined, especially with products that form methemoglobin.

Diagnosis

Because ingredients in cyanide antidote kits can have toxic side effects, accurate diagnosis of cyanide poisoning is important. Currently, diagnosis is based on clinical evaluation, but the presenting symptoms may be confused with exposure to other agents including nerve agents, botulinum toxin, hydrogen sulfide, or carbon monoxide. No rapid diagnostic tests are available for any cyanide-containing compounds.